tbuckley/cabot-search huggingface dataset:
Abstract 14864: Impact of Lifestyle and Cardiometabolic Risk Factors on Atherosclerotic Cardiovascular Diseases Incidence Across Body Weight Categories: A Prospective Study of 321,259 UK Biobank Participants
Authors: Audrey Paulin, Hasanga D Manikpurage, Jean-Pierre Despres, Sebastien Theriault, Benoit Arsenault
Journal: Circulation (2022)

Introduction: Individuals with an elevated body mass index (BMI) are at higher atherosclerotic cardiovascular diseases (ASCVD) risk. While the impact of an elevated BMI on ASCVD risk in individuals who are “metabolically healthy” is still debated, the respective contributions of BMI and actionable lifestyle and cardiometabolic risk factors on ASCVD risk remains largely unknown. We investigated the respective contributions of lifestyle and cardiometabolic risk factors and BMI to ASCVD incidence in apparently healthy individuals. Methods: We developed a cardiovascular health score (CVHS) based on three lifestyle (smoking status, fruits and vegetables consumption and physical activity levels) and six cardiometabolic (blood pressure, HbA1c, LDL-C, HDL-C, C-Reactive Protein and triglyceride levels) parameters. The study sample included 321,259 participants of the UK Biobank, free of ASCVD recruited between 2006 and 2010. As of August 2021, 15,699 of them had incident ASCVD (fatal or nonfatal myocardial infarction, ischemic stroke or cardiac revascularization procedures. The impact of the CVHS on incident ASCVD alone and in BMI categories was assessed using Cox proportional hazards adjusted for age, sex, ethnicity and deprivation. Results: Compared to participants with a very high CVHS (CVHS=9), those with a very low CVHS (CVHS=0) had a higher ASCVD risk (hazard ratio = 12.2 (95% CI, 6.7-22.2, p&lt;0.001). Figure 1 presents the association between the CVHS and hazard ratio for incident ASCVD in four BMI categories. Conclusions: In participants of the UK Biobank, a cardiovascular health score based on lifestyle and cardiometabolic risk factors was strongly associated with incident ASCVD in all BMI categories. The relationship between BMI and ASCVD incidence across CVHS categories was inconsistent. Strategies aimed at improving healthy lifestyle habits and cardiometabolic risk factors may decrease ASCVD risk in everyone, regardless of their body weight.
Abstract 15518: The Effects of High Glucose and Lipoprotein Lipase on Macrophage Regulatory Function
Authors: Ashita Bhatnagar, Francis J Alenghat
Journal: Circulation (2022)

Introduction: Atherosclerosis has an established inflammatory, macrophage(MФ)-mediated component which can be exacerbated by uncontrolled diabetes. However, there are also protective, regulatory MФ processes that can help quell atherosclerosis. Lipoprotein Lipase (LPL) on the MФ surface hydrolyzes circulating triglyceride-rich lipoproteins into glycerol and free fatty acids to provide a non-glucose energy source. Hypothesis: We hypothesized that regulatory MФs have high LPL activity, which could promote fatty acid metabolism to drive inflammation-resolving functions, and that this LPL activity is inhibited by ambient glucose. Methods and Results: MФs were cultured and differentiated from bone marrow harvested from wild-type mice aged 9-16 weeks. Two weeks after harvest, these MФs were polarized with (1) interferon-γ and lipopolysaccharide to stimulate classically-activated, inflammatory MФs or (2) interleukin-4 to stimulate alternatively-activated, regulatory MФs. The resulting phenotypes were validated by canonical transcript markers (Tnfa/Nos2 for inflammatory MФs and Ym1/Arg1 for regulatory MФs) and cell surface markers (CD86 and CD206, respectively). Using a triglyceride analog that fluoresces when cleaved by LPL, we found that regulatory MФs have far greater LPL activity than inflammatory macrophages at baseline (33 ± 2 vs 1 ± 0.2 a.u., p &lt; 0.001, n=8). By varying glucose concentration during the polarization, this effect was most pronounced at normal, physiological concentrations of glucose (5 mM, ~90 mg/dL) and blunted at a high-glucose concentration that can be found in uncontrolled diabetes (25 mM). We also report on lipoxygenase expression and specialized pro-resolving mediator production as effector functions downstream of LPL activity in regulatory MФs. Conclusions: Taken together, our findings support a model in which regulatory MФs are programmed to utilize LPL to drive the inflammation-resolving phenotype and that this process works best at low, physiologic glucose concentrations. Future translational work will investigate whether a lack of LPL-mediated regulatory MФ function is a reason why patients with uncontrolled diabetes have higher atherosclerotic burden and plaque instability.
Abstract 15321: MicroRNA Mir-378-3p is a Novel Regulator of Endothelial Autophagy and Function
Authors: Shuhan Bu, Sepideh Nikfarjam, Hien Chi Nguyen, Berk Rasheed, Rohan Singh, Mohammad Qadura, Jefferson C Frisbee, Krishna Singh
Journal: Circulation (2022)

Introduction: Autophagy maintains cellular homeostasis by degradation of unnecessary proteins for their recycling and reuse. MicroRNAs (miRNAs) regulate various biological processes including autophagy. MiRNA and autophagy both regulate endothelial function, however, role of miRNAs in endothelial autophagy and function is unknown. Methods and Results: To understand the role of miRNAs in endothelial autophagy, autophagy was genetically inhibited via ATG7 (autophagy-related gene 7) silencing in Human Umbilical Vein Endothelial Cells (HUVECs) and then a miRNA array was performed, which showed miR-378-3p as the most up-regulated miRNA. Pharmacological (via chloroquine treatment) inhibition of autophagy in HUVECs resulted in significant upregulation of miR-378a-3p. Autophagy activation via starvation in HUVECs significantly reduced miR-378a-3p expression. Next, we over-expressed miR-378a-3p (via mimic) in HUVECs and measured autophagy and endothelial function. MiR-378a-3p overexpression was associated with impaired autophagy (reduced LC3-II/LC3-I ratio), reduced proliferation, and increased migration in HUVECs. At the molecular level, miR-378a-3p overexpression was associated with reduced eNOS expression at both transcript and protein levels in HUVECs. MiR-378a-3p inhibition (via antagomir) led to reduced cell migration and upregulation of eNOS in HUVECs. In-silico study identified PDIA4 as a potential target of miR-378-3p, and our qPCR data and immunoblotting data confirmed increased and reduced PDIA4 expression in mimics and antagomir-transfected HUVECs, respectively. We then inhibited autophagy using chloroquine (50uM) and observed significantly reduced PDIA4 expression. Inhibition of PDIA4 expression via silencing inhibited autophagic flux indicated by reduced LC3-II/LC3-I in HUVECs. Conclusions: Our findings, for the first time, show an inverse relationship between miR-378a-3p expression and endothelial autophagy and endothelial function. PDIA4 was identified as a molecular target for miR-378a-3p in endothelial cells, which revealed PDIA4’s potential role in endothelial autophagy. Our data demonstrate that miR-378-3p regulates endothelial autophagy and function via modulating PDIA4 expression.
Abstract 14471: Cardiac Sarcoidosis Presenting With Hiccups - A Case Report
Authors: Ivan Cancarevic, Muhammad Ghallab, Zarwa Idrees, Tracey O'Brien, Frantzcess Compas
Journal: Circulation (2022)

Introduction: Sarcoidosis is a multi-system disorder of unknown etiology that is commonly associated with hilar lymphadenopathy and granulomas. Cardiac involvement is less common, however, sarcoidosis is a known cause of restrictive cardiomyopathy. It typically presents as new-onset arrhythmias or heart failure, although cases of sudden cardiac death have been reported. Case presentation: We present a case of a 56-year-old male with a known history of pulmonary sarcoidosis, not on any active treatment, who presented to the emergency department with one week of continuous hiccups every few seconds associated with non-exertional dyspnea. Initial CT scan of the chest showed multiple stellate-like ground-glass opacities and progression of bronchiectasis. Troponins were negative. On the initial EKG, he was found to be in atrial flutter and was admitted to the general medical floor. He was given baclofen and the hiccups resolved over the next 24 hours. Cardiology was consulted for suspected cardiac sarcoidosis and they recommended transferring the patient to the tertiary care center for further evaluation. Upon arrival, the patient underwent catheter ablation for atrial flutter and he returned to the sinus rhythm after the procedure. The initial nuclear scan with gallium was not suggestive of cardiac sarcoidosis, however, subsequent cardiac MRI showed cardiac involvement. Due to the high risk of arrhythmias, the patient was scheduled for implantable cardioverter defibrillator placement before discharge. Treatment with steroids was deferred until after the PET scan could be completed. The patient was discharged in stable condition and interrogation of the device found it to be well functioning and with no significant arrhythmias noted. Conclusions: Presentation of cardiac sarcoidosis can be variable and should be considered in any patient with a known history of sarcoidosis who presents with atypical symptoms at or above the level of the diaphragm, such as hiccups or with new-onset arrhythmias.
Abstract 14704: Comparison of Anticoagulation Strategies for Epicardial Access in Ventricular Tachycardia Catheter Ablation
Authors: Jorge Romero, Isabella Alviz, Alejandro Velasco, Mohamed Gabr, Joan Rodriguez-Taveras, Daniel Rodriguez, Marta Lorente Ros, Luis Cerna, Jorge Marin, Mauricio Duque, Kartikeya P Dave, KARTIKEYA P DAVE, JOSE MATIAS, Jose Matias, Jose Matias, Domenico G Della Rocca, Andrea Natale, Sanghamitra Mohanty, Juan C Diaz, Luigi Di Biase
Journal: Circulation (2022)

Introduction: Percutaneous epicardial access (EpiAcc) is frequently required for endo-epicardial ablation of ventricular tachycardia (VT), especially in ischemic cardiomyopathy, where it has been demonstrated to increase success rate. For patients who have indications for chronic oral anticoagulation (OAC), this often poses a challenge due to potential risks of procedural complications. We sought to assess the safety and outcomes of epicardial VT ablation on uninterrupted OAC compared to off anticoagulation. Methods: In this multicenter study, we retrospectively analyzed patients with ischemic cardiomyopathy and VT who underwent endo-epicardial ablation with EpiAcc. The study group included patients who underwent ablation either under uninterrupted OAC or off anticoagulation. Procedural data, outcomes, and complication rates were analyzed for comparison of both groups. Results: Overall, we analyzed 135 patients who underwent VT ablation via EpiAcc; 55 under full-dose uninterrupted AC and 80 off AC. There was no difference in procedure-related complications between both groups (1.8% vs 2.5%, p=0.09). There was no major bleeding requiring transfusion in any group. There was no difference in risk of cardiac tamponade between both groups (0% vs 0%, p=1). The rate of groin hematoma was 1.8% vs 1.3%, p=0.087). No thromboembolic events were reported. Conclusion: Epicardial VT ablation on uninterrupted OAC is a safe alternative to off AC, with no additional risk of life-threatening complications, thus preventing the possibility of thromboembolic events in patients who have an indication for chronic AC. 1
Abstract 15880: Detection of an Acute Pulmonary Embolism in the Home Bed Using Adherence-Independent Home Monitoring
Authors: David Torres Barba, Nicholas Harrington, Parag Agnihotri, Kevin King
Journal: Circulation (2022)

Acute pulmonary embolism classically presents with dyspnea, tachypnea, and hypoxia, but self-recognition of symptoms and clinical findings is often challenging. This is particularly true in elder patients or those with cognitive impairments. Digital health technologies offer opportunities to remotely detect pre-symptomatic illness. We present a prodrome of an acute pulmonary embolism as it emerges in the home during continuous respiratory monitoring using a non-contact adherence-independent home bed sensor. The patient is an 85-year-old woman who is morbidly obese, has limited mobility, and multiple comorbidities including a recent diagnosis of atrial fibrillation for which she was prescribed anticoagulation but has not yet initiated. As part of an observational study, nocturnal respiratory rates (NRR) were longitudinally monitored in her home bed using a non-contact, adherence-independent bed sensor. Eight days prior to admission, increasing NRR prompted a patient call to family who noted no acute symptomatic changes. During the call it was discovered she had not been started on apixaban. On subsequent days, persistently elevated NRR prompted a second phone call 4 days prior to admission (PTA), where again no acute symptoms were noted. Anticoagulation still had not been started at that time. NRR worsened further on days following the second call prompting a home visit by an RN who found the patient dyspneic, tachypneic in the high 20s, and hypoxic with oxygen saturations in the 80s, prompting a transfer to the emergency department for further evaluation. She was eventually diagnosed with an acute pulmonary embolism. After a week-long hospitalization, the patient was discharged on adequate anticoagulation therapy.This case suggests that adherence-independent home bed monitoring of nocturnal respiratory rate may enable early detection of chronic volume overload and acute pulmonary embolism, potentially facilitating early intervention.
Abstract 14822: Lipoprotein (a) is a Residual Risk Factor of Aortic Valve Calcification in Patients With High Risk of Atherosclerotic Disease
Authors: Shusuke Yagi, Munkhtsetseg Tserensonom, Masataka Sata
Journal: Circulation (2022)

Introduction: The number of patients with aortic valve stenosis which results from aortic valve calcification (AVC), has been increasing in the elderly population. The risk factors of AVC include diabetes, dyslipidemia, and hypertension. However, control of these risk factors has not resulted in a decreased incidence of AVC. Increased Lipoprotein (LP) (a) and oxidized low-density lipoprotein (LDL), or decreased omega 3-fatty acids, are the candidates for serum biomarkers of residual risk factors. However, the most contributable risk factors for AVC has not been identified. Methods: We enrolled a total of 618 patients who underwent coronary angiography by computed tomography because of suspicion of coronary artery disease (CAD). Calcium scores were calculated using imaging software (3mensio Medical Imaging) and existence of coronary stenosis was evaluated. Patients who were suspected of having significant coronary stenosis underwent coronary angiography to confirm the existence of ischemic heart disease. Patients were evaluated for residual risk factors including Lp(a), oxidized LDL, omega 3- and 6-fatty acids, and C-reactive protein in addition to markers of conventional risk factors. Result: The calcium score in patients who received aortic valve replacement was significantly higher than that in patients who did not undergo AVR. There were no difference between the calcium scores in patients with CAD and those without CAD. Univariate analysis showed that the calcium score was associated with levels of Lp(a) (P&lt;0.01) but not with omega 3- and 6-fatty acids, oxidative LDL, hemoglobin A1c, LDL- and HDL-cholesterol, triglycerides, and C-reactive protein. Multivariate analysis showed that increased Lp(a) and age were independently correlated with the calcium score (P&lt;0.01), but sex and the existence of other conventional risk factors including hypertension, dyslipidemia, and chronic kidney disease were not. Conclusion: Serum Lp(a) is a potent risk factor for AVC in patients with high risk of atherosclerosis. Lowering Lp(a) may be a potential strategy for prevention of AVC. Intervention studies involving methods of lowering Lp(a) are needed to confirm the results.
Abstract 14889: Association of Calcium Channel Blockers With Mortality and Hospitalization Rate In Sars-Cov-2 Patients
Authors: Aaron Douen, Samuel Tan, Marc Sukhoo-Pertab, Wenchy Siu, Jeremy Oh, Wesley Romney, Prakash Ramdass, Tatiana Echeverry, George Juang, Aleksandre Toreli
Journal: Circulation (2022)

Introduction: Literature has shown that calcium metabolism mediates the body’s defense against viral pathogens. In particular, studies have found SARS-CoV-2 to use calcium to assist entry and replication in host cells. Hypothesis: The use of CCBs are associated with decreased mortality and hospitalization in SARS-CoV-2 positive patients. Methods: A retrospective chart review of patients 18 years and older with a positive SARS-CoV-2 polymerase chain reaction test between March 2020 and April 2021. Patients were categorized based on their use and non-use of CCB. The primary outcomes were all-cause mortality and hospitalization. Secondary outcomes were acute kidney injury, hypotension, intubation, myocardial infarction, systolic heart failure, ventricular tachycardia (VT), and ventricular fibrillation (VF). Multivariate logistic regression was used to adjust for baseline characteristics. Results: We identified 1,402 patients taking CCB and 21,674 patients not taking CCB who tested positive for SARS- CoV-2. The baseline characteristic incidence was 370 (26.4%) for coronary artery disease, 262 (18.7%) for heart failure, 1402 (100%) for hypertension in patients taking CCBs. Secondary outcome incidence was 85 (6.1%) for myocardial infarction, 257 (18.3%) for hypotension, and 100 (7.1%) for systolic heart failure in patients taking CCBs. After adjusting for comorbidities using logistic regression, OR was 0.605 (95% Confidence Interval [CI]: 0.519-0.705; p &lt; 0.001) for all-cause mortality, and 27.641 (95% CI: 24.396-31.319; p&lt;0.001) for hospitalization rate. The CCB group had significantly decreased adjusted OR for all secondary outcomes (p&lt;0.001) except for VT (p&lt;0.425) and VF (p &lt;1.00). Conclusions: The incidence of cardiovascular outcomes and baseline cardiovascular risk factors were significantly greater in SARS-CoV-2 positive patients taking CCB. SARS-CoV-2 positive patients in the CCB group were associated with decreased all-cause mortality, myocardial infarction, and systolic heart failure. However, the CCB group had a significantly increased association with hospitalization. Therefore, when indicated, clinicians should consider using CCB in SARS-CoV-2 patients, especially those with cardiovascular risk factors.
Abstract 14479: Prolonged Decrease in Endothelial Cell (EC)-Specific Mitochondrial ROS Results in Mitochondrial Dysfunction in Coronary EC and Cardiac Hypertrophy in Post-AMI Animals
Authors: Rayane Brinck Teixeira, Peng Zhang, Frank W Sellke, Ruhul Abid
Journal: Circulation (2022)

Introduction: Reducing mitochondrial ROS (mito-ROS) has been a novel approach for improving cardiac function. Here, we evaluated the effect of prolonged decrease in EC-specific mito-ROS on post-acute myocardial infarction (AMI) coronary angiogenesis and cardiac function. Hypothesis: We hypothesized that a prolonged decrease in EC-specific mito-ROS contributes to mitochondrial dysfunction in coronary EC resulting in post-AMI maladaptive cardiac remodeling. Methods: We used an EC-specific, tetracycline-controlled, transgenic MnSOD overexpression (MnSOD-OE) model. After 16 weeks of MnSOD-OE, mice underwent ligation of left anterior coronary artery (AMI). 28 days post-AMI, ejection fraction (EF), fractional shortening (FS), and left ventricle (LV) mass were determined by echocardiography (n=8/group). Isolated mouse heart ECs (MHEC) were evaluated by Seahorse for mitochondrial function and by western blot for cell signaling. Data were analyzed by Student’s t test. A p -value ≤0.05 was considered statistically significant. Results: MnSOD-OE mice showed 33% decrease (44.4±2.3 vs. 29.7±3.5) in EF and 35% decrease (21.7±1.2 vs. 14.2±1.7) in FS, compared to control. LV mass was increased by 51% (76.4±1.8 vs. 115.1±12.33 mg) in MnSOD-OE heart. LV end systolic and diastolic areas were increased in MnSOD-OE, by 2-fold (5.8±0.4 vs. 12.6±1.8) and 1.7-fold (9.8±0.5 vs. 16.8±1.6 mm 2 ), respectively. MnSOD-OE MHEC showed a reduction in mitochondrial maximal and spare respiration capacities, and decreased activation of Akt by 25% and ERK by 23%. Conclusions: Prolonged MnSOD-OE impaired mitochondrial respiration and inhibited Akt and ERK signaling in MHEC. These changes were associated with maladaptive remodeling post-AMI, including cardiac hypertrophy, LV dilatation, and systolic dysfunction. Together, these findings suggest that prolonged decrease in mito-ROS has detrimental effects on coronary EC resulting in maladaptive post-AMI cardiac remodeling.
Abstract 14785: Predictors of In-Hospital Mortality in Coronary Artery Aneurysm Patients: An Insight From the National Inpatient Sample Database
Authors: Ghulam Mujtaba Ghumman, Jay Shah, Maen Al-Dabbas, Muhammad Shayan Khan, Kritika Luthra, Amir Khan, Muhammad Ahsan, Heminder Singh, Mohammed Taleb, Sohail Ali
Journal: Circulation (2022)

Background: There is limited literature on the mortality outcome of coronary artery aneurysms (CAA). The purpose was to study the baseline characteristics, associated co-morbidities, and in-hospital mortality in CAA patients using the Healthcare Cost and Utilization Project National Inpatient Sample database. Methods: The Healthcare Cost and Utilization Project administrative longitudinal database contains encounter-level information on inpatient stays, emergency department visits, and ambulatory surgery in all U.S. hospitals. We performed a cross-sectional analysis on 10230 patients diagnosed with CAA during hospitalization from January 2016 to December 2018. The primary outcome was in-hospital mortality. Results: Of the total patient population, 10230 patients were found to have CAA. All patients with ages ≥ 18 were included in the study (8660). Hypertension, diabetes mellitus, and peripheral vascular disease were predominant co-morbidities. The observed overall in-hospital mortality was 2.9% (251 patients out of 8660). The highest mortality was observed in patients with acute myocardial infarction (adjusted odds ratio: 80.9; 95% confidence interval: 51.9 to 126.1; p-value &lt; 0.01). The age group &gt;80 years had higher mortality when compared to the age group &lt;40 years (adjusted odds ratio: 9.1; 95% confidence interval: 2.9 to 29.3; p-value &lt; 0.00). Smoking (adjusted odds ratio: 46.6; 95% confidence interval: 31.3 to 69.2; p-value &lt; 0.01) and peripheral vascular disease (adjusted odds ratio: 4.0; 95% confidence interval: 2.7 to 6.0; p-value &lt; 0.01) also had a significant impact on mortality (Table 1,2). Conclusion: Our analysis showed higher mortality in CAA with increasing age and in patients who developed acute myocardial infarction, with smoking and peripheral vascular disease also having a significant impact.